We have recently shown that thymus-dependent differentiation results in the formation of at least three functionally different subclasses of T cells, identifiable by different patterns of cell-surface Ly determinants (14,15). The use of these surface components for separating T cell subclasses represents a direct approach to delineating the life history of functionally different T cell subclasses and analyzing their contributions to different forms of immune responses. Using antisera prepared against five Ly antigens (Ly-1, Ly-2, and Ly-3, as well as newly developed sera to Ly-5 and Ly-6), in combination with C57BL/6 mice congenic at the different Ly loci, we propose to establish the following: (a) the immunobiologic properties of subclasses of T cells that express different surface patterns of Ly antigens, particularly with respect to T cells that mediate helper and suppressor activity, delayed-type hypersensitivity, and cytotoxicity; (b) the developmental relationship between different Ly ion T cell subclasses; (c) the contribution of cell-surface Ly molecules to the cytotoxic and helper response; (d) the influence of H-linked genes upon the differentiation of helper and suppressor Ly ion subclasses; (e) the role of different Ly ion T cell subclass in the induction and maintenance of tolerance; (f) the Ia/Ly surface profiles of functional subclasses of T lymphocytes using antisera specific for newly-identified Ly determinants as well as antisera that define I region (Ia) antigens.